A Study to Evaluate the Safety, Tolerability, and PK in Healthy Volunteers and HCV Genotype 1 Infected Patients

NCT ID: NCT01523990

Last Updated: 2014-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

135 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-10-31

Study Completion Date

2013-07-31

Brief Summary

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A Safety Study to Evaluate the Safety, Tolerability, and Pharmacokinetics in HCV Genotype 1 Infected Patients

Detailed Description

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A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study in Healthy East Asian and Caucasian Volunteers to Evaluate the Safety, Tolerability, and Pharmacokinetics Profiles of Single and Multiple Ascending Oral Doses of TG-2349, and Followed by a Dose-Ranging Study in Hepatitis C Genotype 1 Infected Patients.

Conditions

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Healthy Hepatitis C, Chronic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Panel I (TG-2349)

Sequential single oral dose taken by healthy East and Caucasian volunteers from 50 mg (fasted) to 50 mg (fed) of TG-2349 with 1 week follow-up after each dosage. A washout period of at least 10 days between the 1st and the 2nd dose is required.

Group Type EXPERIMENTAL

TG-2349

Intervention Type DRUG

Supplied as oral liquid formulation in pre-filled glass syringe. Two dose strengths, 25 mg TG-2349 (25 mg/mL in PEG 400, 1.1 mL fill) and 200 mg TG-2349 (50 mg/mL in PEG 400, 4.1 mL fill), are filled into 5-mL type 1 glass syringes. Required doses during clinical study are to be dispensed using the combination of the two dose units. The entire content of the syringe is to be taken by mouth.

Panel I (placebo)

Sequential single oral dose taken by healthy East and Caucasian volunteers from 50 mg (fasted) to 50 mg (fed) of placebo with 1 week follow-up after each dosage. A washout period of at least 10 days between the 1st and the 2nd dose is required.

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

Available in two different unit doses, 1.1 mL and 4.1 mL PEG 400 in 5-mL type 1 glass syringes. They are identical in appearance and similar in weight to TG-2349 oral liquid syringes.

Panel II (TG-2349)

Sequential single oral dose taken by healthy East and Caucasian volunteers from 100 mg (fasted) to 100 mg (fed) of TG-2349 with 1 week follow-up after each dosage. A washout period of at least 10 days between the 1st and the 2nd dose is required.

Group Type EXPERIMENTAL

TG-2349

Intervention Type DRUG

Supplied as oral liquid formulation in pre-filled glass syringe. Two dose strengths, 25 mg TG-2349 (25 mg/mL in PEG 400, 1.1 mL fill) and 200 mg TG-2349 (50 mg/mL in PEG 400, 4.1 mL fill), are filled into 5-mL type 1 glass syringes. Required doses during clinical study are to be dispensed using the combination of the two dose units. The entire content of the syringe is to be taken by mouth.

Panel II (placebo)

Sequential single oral dose taken by healthy East and Caucasian volunteers from 100 mg (fasted) to 100 mg (fed) of placebo with 1 week follow-up after each dosage. A washout period of at least 10 days between the 1st and the 2nd dose is required.

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

Available in two different unit doses, 1.1 mL and 4.1 mL PEG 400 in 5-mL type 1 glass syringes. They are identical in appearance and similar in weight to TG-2349 oral liquid syringes.

Panel III (TG-2349)

Sequential single oral dose taken by healthy East and Caucasian volunteers from 200 mg (fasted or fed) to 400 mg (fasted or fed) of TG-2349 with 1 week follow-up after each dosage. A washout period of at least 10 days between the 1st and the 2nd dose is required.

Group Type EXPERIMENTAL

TG-2349

Intervention Type DRUG

Supplied as oral liquid formulation in pre-filled glass syringe. Two dose strengths, 25 mg TG-2349 (25 mg/mL in PEG 400, 1.1 mL fill) and 200 mg TG-2349 (50 mg/mL in PEG 400, 4.1 mL fill), are filled into 5-mL type 1 glass syringes. Required doses during clinical study are to be dispensed using the combination of the two dose units. The entire content of the syringe is to be taken by mouth.

Panel III (placebo)

Sequential single oral dose taken by healthy East and Caucasian volunteers from 200 mg (fasted or fed) to 400 mg (fasted or fed) of placebo with 1 week follow-up after each dosage. A washout period of at least 10 days between the 1st and the 2nd dose is required.

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

Available in two different unit doses, 1.1 mL and 4.1 mL PEG 400 in 5-mL type 1 glass syringes. They are identical in appearance and similar in weight to TG-2349 oral liquid syringes.

Panel IV (TG-2349)

Sequential single oral dose taken by healthy East and Caucasian volunteers from 600 mg (fasted or fed) to 800 mg (fasted or fed) of TG-2349 with 1 week follow-up after each dosage. A washout period of at least 10 days between the 1st and the 2nd dose is required.

Group Type EXPERIMENTAL

TG-2349

Intervention Type DRUG

Supplied as oral liquid formulation in pre-filled glass syringe. Two dose strengths, 25 mg TG-2349 (25 mg/mL in PEG 400, 1.1 mL fill) and 200 mg TG-2349 (50 mg/mL in PEG 400, 4.1 mL fill), are filled into 5-mL type 1 glass syringes. Required doses during clinical study are to be dispensed using the combination of the two dose units. The entire content of the syringe is to be taken by mouth.

Panel IV (placebo)

Sequential single oral dose taken by healthy East and Caucasian volunteers from 600 mg (fasted or fed) to 800 mg (fasted or fed) of placebo with 1 week follow-up after each dosage. A washout period of at least 10 days between the 1st and the 2nd dose is required.

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

Available in two different unit doses, 1.1 mL and 4.1 mL PEG 400 in 5-mL type 1 glass syringes. They are identical in appearance and similar in weight to TG-2349 oral liquid syringes.

Panel V (TG-2349)

Oral dose taken once daily for 5 consecutive days at dose level of 100 mg taken by healthy East and Caucasian volunteers .

Group Type EXPERIMENTAL

TG-2349

Intervention Type DRUG

Supplied as oral liquid formulation in pre-filled glass syringe. Two dose strengths, 25 mg TG-2349 (25 mg/mL in PEG 400, 1.1 mL fill) and 200 mg TG-2349 (50 mg/mL in PEG 400, 4.1 mL fill), are filled into 5-mL type 1 glass syringes. Required doses during clinical study are to be dispensed using the combination of the two dose units. The entire content of the syringe is to be taken by mouth.

Panel V (placebo)

Oral dose taken once daily for 5 consecutive days at dose level of 100 mg taken by healthy East and Caucasian volunteers .

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

Available in two different unit doses, 1.1 mL and 4.1 mL PEG 400 in 5-mL type 1 glass syringes. They are identical in appearance and similar in weight to TG-2349 oral liquid syringes.

Panel VI (TG-2349)

Oral dose taken once daily for 5 consecutive days at dose level of 200 mg taken by healthy East and Caucasian volunteers .

Group Type EXPERIMENTAL

TG-2349

Intervention Type DRUG

Supplied as oral liquid formulation in pre-filled glass syringe. Two dose strengths, 25 mg TG-2349 (25 mg/mL in PEG 400, 1.1 mL fill) and 200 mg TG-2349 (50 mg/mL in PEG 400, 4.1 mL fill), are filled into 5-mL type 1 glass syringes. Required doses during clinical study are to be dispensed using the combination of the two dose units. The entire content of the syringe is to be taken by mouth.

Panel VI (placebo)

Oral dose taken once daily for 5 consecutive days at dose level of 200 mg taken by healthy East and Caucasian volunteers .

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

Available in two different unit doses, 1.1 mL and 4.1 mL PEG 400 in 5-mL type 1 glass syringes. They are identical in appearance and similar in weight to TG-2349 oral liquid syringes.

Panel VII (TG-2349)

Oral dose taken once daily for 5 consecutive days at dose level of 400 mg taken by healthy East and Caucasian volunteers .

Group Type EXPERIMENTAL

TG-2349

Intervention Type DRUG

Supplied as oral liquid formulation in pre-filled glass syringe. Two dose strengths, 25 mg TG-2349 (25 mg/mL in PEG 400, 1.1 mL fill) and 200 mg TG-2349 (50 mg/mL in PEG 400, 4.1 mL fill), are filled into 5-mL type 1 glass syringes. Required doses during clinical study are to be dispensed using the combination of the two dose units. The entire content of the syringe is to be taken by mouth.

Panel VII (placebo)

Oral dose taken once daily for 5 consecutive days at dose level of 400 mg taken by healthy East and Caucasian volunteers .

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

Available in two different unit doses, 1.1 mL and 4.1 mL PEG 400 in 5-mL type 1 glass syringes. They are identical in appearance and similar in weight to TG-2349 oral liquid syringes.

Panel VIII (TG-2349)

Oral dose taken once daily for 5 consecutive days at dose level of 600 mg taken by healthy East and Caucasian volunteers .

Group Type EXPERIMENTAL

TG-2349

Intervention Type DRUG

Supplied as oral liquid formulation in pre-filled glass syringe. Two dose strengths, 25 mg TG-2349 (25 mg/mL in PEG 400, 1.1 mL fill) and 200 mg TG-2349 (50 mg/mL in PEG 400, 4.1 mL fill), are filled into 5-mL type 1 glass syringes. Required doses during clinical study are to be dispensed using the combination of the two dose units. The entire content of the syringe is to be taken by mouth.

Panel VIII (placebo)

Oral dose taken once daily for 5 consecutive days at dose level of 600 mg taken by healthy East and Caucasian volunteers .

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

Available in two different unit doses, 1.1 mL and 4.1 mL PEG 400 in 5-mL type 1 glass syringes. They are identical in appearance and similar in weight to TG-2349 oral liquid syringes.

Panel IX (TG-2349)

Oral dose taken once daily for 3 consecutive days at dose level of 200 mg (fed) taken by HCV genotype 1 (including subtypes 1a or 1b or mixed 1a/1b) infected patients.

Group Type EXPERIMENTAL

TG-2349

Intervention Type DRUG

Supplied as oral liquid formulation in pre-filled glass syringe. Two dose strengths, 25 mg TG-2349 (25 mg/mL in PEG 400, 1.1 mL fill) and 200 mg TG-2349 (50 mg/mL in PEG 400, 4.1 mL fill), are filled into 5-mL type 1 glass syringes. Required doses during clinical study are to be dispensed using the combination of the two dose units. The entire content of the syringe is to be taken by mouth.

Panel IX (placebo)

Oral dose taken once daily for 3 consecutive days at dose level of 200 mg (fed) taken by HCV genotype 1 (including subtypes 1a or 1b or mixed 1a/1b) infected patients.

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

Available in two different unit doses, 1.1 mL and 4.1 mL PEG 400 in 5-mL type 1 glass syringes. They are identical in appearance and similar in weight to TG-2349 oral liquid syringes.

Panel X (TG-2349)

Oral dose taken once daily for 3 consecutive days at dose level of 400 mg (fed) taken by HCV genotype 1 (including subtypes 1a or 1b or mixed 1a/1b) infected patients.

Group Type EXPERIMENTAL

TG-2349

Intervention Type DRUG

Supplied as oral liquid formulation in pre-filled glass syringe. Two dose strengths, 25 mg TG-2349 (25 mg/mL in PEG 400, 1.1 mL fill) and 200 mg TG-2349 (50 mg/mL in PEG 400, 4.1 mL fill), are filled into 5-mL type 1 glass syringes. Required doses during clinical study are to be dispensed using the combination of the two dose units. The entire content of the syringe is to be taken by mouth.

Panel X (placebo)

Oral dose taken once daily for 3 consecutive days at dose level of 400 mg (fed) taken by HCV genotype 1 (including subtypes 1a or 1b or mixed 1a/1b) infected patients.

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

Available in two different unit doses, 1.1 mL and 4.1 mL PEG 400 in 5-mL type 1 glass syringes. They are identical in appearance and similar in weight to TG-2349 oral liquid syringes.

Panel XI (TG-2349)

Oral dose taken once daily for 3 consecutive days at dose level of 600 mg (fed) taken by HCV genotype 1 (including subtypes 1a or 1b or mixed 1a/1b) infected patients.

Group Type EXPERIMENTAL

TG-2349

Intervention Type DRUG

Supplied as oral liquid formulation in pre-filled glass syringe. Two dose strengths, 25 mg TG-2349 (25 mg/mL in PEG 400, 1.1 mL fill) and 200 mg TG-2349 (50 mg/mL in PEG 400, 4.1 mL fill), are filled into 5-mL type 1 glass syringes. Required doses during clinical study are to be dispensed using the combination of the two dose units. The entire content of the syringe is to be taken by mouth.

Panel XI (placebo)

Oral dose taken once daily for 3 consecutive days at dose level of 600 mg (fed) taken by HCV genotype 1 (including subtypes 1a or 1b or mixed 1a/1b) infected patients.

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

Available in two different unit doses, 1.1 mL and 4.1 mL PEG 400 in 5-mL type 1 glass syringes. They are identical in appearance and similar in weight to TG-2349 oral liquid syringes.

Panel XII (TG-2349)

Oral dose taken once daily for 3 consecutive days at dose level of 600 mg (fed) taken by HCV genotype 2 infected, treatment-naive patients.

Group Type EXPERIMENTAL

TG-2349

Intervention Type DRUG

Supplied as oral liquid formulation in pre-filled glass syringe. Two dose strengths, 25 mg TG-2349 (25 mg/mL in PEG 400, 1.1 mL fill) and 200 mg TG-2349 (50 mg/mL in PEG 400, 4.1 mL fill), are filled into 5-mL type 1 glass syringes. Required doses during clinical study are to be dispensed using the combination of the two dose units. The entire content of the syringe is to be taken by mouth.

Panel XIII (TG-2349)

Oral dose taken once daily for 3 consecutive days at dose level of 600 mg (fed) taken by HCV genotype 3 infected, treatment-naive patients.

Group Type EXPERIMENTAL

TG-2349

Intervention Type DRUG

Supplied as oral liquid formulation in pre-filled glass syringe. Two dose strengths, 25 mg TG-2349 (25 mg/mL in PEG 400, 1.1 mL fill) and 200 mg TG-2349 (50 mg/mL in PEG 400, 4.1 mL fill), are filled into 5-mL type 1 glass syringes. Required doses during clinical study are to be dispensed using the combination of the two dose units. The entire content of the syringe is to be taken by mouth.

Panel XIV (TG-2349)

Oral dose taken once daily for 3 consecutive days at dose level of 600 mg (fed) taken by HCV genotype 4 infected, treatment-naive patients.

Group Type EXPERIMENTAL

TG-2349

Intervention Type DRUG

Supplied as oral liquid formulation in pre-filled glass syringe. Two dose strengths, 25 mg TG-2349 (25 mg/mL in PEG 400, 1.1 mL fill) and 200 mg TG-2349 (50 mg/mL in PEG 400, 4.1 mL fill), are filled into 5-mL type 1 glass syringes. Required doses during clinical study are to be dispensed using the combination of the two dose units. The entire content of the syringe is to be taken by mouth.

Panel XV (TG-2349)

Oral dose taken once daily for 3 consecutive days at dose level of 600 mg (fed) taken by HCV genotype 5 infected, treatment-naive patients.

Group Type EXPERIMENTAL

TG-2349

Intervention Type DRUG

Supplied as oral liquid formulation in pre-filled glass syringe. Two dose strengths, 25 mg TG-2349 (25 mg/mL in PEG 400, 1.1 mL fill) and 200 mg TG-2349 (50 mg/mL in PEG 400, 4.1 mL fill), are filled into 5-mL type 1 glass syringes. Required doses during clinical study are to be dispensed using the combination of the two dose units. The entire content of the syringe is to be taken by mouth.

Panel XVI (TG-2349)

Oral dose taken once daily for 3 consecutive days at dose level of 600 mg (fed) taken by HCV genotype 6 infected, treatment-naive patients.

Group Type EXPERIMENTAL

TG-2349

Intervention Type DRUG

Supplied as oral liquid formulation in pre-filled glass syringe. Two dose strengths, 25 mg TG-2349 (25 mg/mL in PEG 400, 1.1 mL fill) and 200 mg TG-2349 (50 mg/mL in PEG 400, 4.1 mL fill), are filled into 5-mL type 1 glass syringes. Required doses during clinical study are to be dispensed using the combination of the two dose units. The entire content of the syringe is to be taken by mouth.

Interventions

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TG-2349

Supplied as oral liquid formulation in pre-filled glass syringe. Two dose strengths, 25 mg TG-2349 (25 mg/mL in PEG 400, 1.1 mL fill) and 200 mg TG-2349 (50 mg/mL in PEG 400, 4.1 mL fill), are filled into 5-mL type 1 glass syringes. Required doses during clinical study are to be dispensed using the combination of the two dose units. The entire content of the syringe is to be taken by mouth.

Intervention Type DRUG

placebo

Available in two different unit doses, 1.1 mL and 4.1 mL PEG 400 in 5-mL type 1 glass syringes. They are identical in appearance and similar in weight to TG-2349 oral liquid syringes.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* East Asian or Caucasian subjects, male or female, and 18 to 65 years of age inclusive
* Body mass index (BMI) in the range of 19.0 to 30.0 kg/m2 and body weight ≥ 50 kg inclusive
* In generally good physical and mental health status on the basis of a medical history review, medical evaluation including vital signs and physical examination, 12-lead ECG, and laboratory results at screening
* For females, one of the following criteria must be fulfilled:

1. At least 1 year post menopausal, or
2. Surgically sterile, or
3. Willing to use a double barrier method \[intrauterine device (IUD) plus condom, spermicidal gel plus condom\] of contraception from screening until 30 days after the last dose of study drug
* Males must be willing to use a reliable form of contraception (use of a condom or a partner fulfilling the above criteria) from screening until 30 days after the last dose of study drug
* Willing to abstain from caffeine- or xanthine-containing beverages, including coffee and tea, alcohol, grapefruit juice, and Seville oranges during the stay-on-site period
* Willing and able to provide written informed consent

Exclusion Criteria

* Positive serological test for IgM anti-HAV antibody, HBsAg or anti-HCV antibody at screening
* Positive ELISA test for HIV-1 or HIV-2 at screening
* Any abnormal laboratory values at screening: Hemoglobin (Hb) \<12.0g/dL for women and \<13.0g/dL for men, white blood cell count (WBC) \<3,000 cells/mm3, absolute neutrophil count \<1,500 cells/mm3, platelet count \<100,000 cells/mm3, serum creatinine ≥ 2 mg/dL, ALT or AST levels ≥ 2 xULN, total bilirubin

≥ 1.5 x ULN, INR (International Normalized Ratios for prothrombin time) ≥ 1.5 xULN
* Any abnormal laboratory values that are considered clinically significant by the Investigator at screening
* QTcF greater than 450 msec for females and 430 msec for males at screening
* History of renal, hepatic impairment, stomach or intestinal surgery or resection, malabsorption syndrome
* History of seizures, epilepsy, cardiovascular, diabetes or cancer (except basal cell carcinoma)
* History or family history of prolonged QT interval or family history of sudden cardiac death at a young age
* History of drug allergy or hypersensitivity, especially to sulfa drugs
* History or evidence of abuse of alcohol, barbiturate, amphetamine, recreational or narcotic drug use within 6 months prior to first dose of study drug administration
* Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of a psychiatric illness, or have any history of suicide attempt or depression
* Anemia or blood/plasma donation within 30 days prior to first dose of study drug administration
* Pregnant or breast-feeding
* Use of tobacco or nicotine-containing products within 30 days prior to first dose of study drug administration
* Use of concomitant medication, including herbal remedies, and dietary supplements (except for paracetamol/acetaminophen, ibuprofen and hormonal contraceptives) within 14 days prior to first dose of study drug administration
* Received any other investigational drug within 30 days prior to first dose of study drug administration
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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TaiGen Biotechnology Co., Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Nicole Sims, DO

Role: PRINCIPAL_INVESTIGATOR

WCCT

Locations

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WCCT

Cypress, California, United States

Site Status

Countries

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United States

Other Identifiers

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TG-2349-01

Identifier Type: -

Identifier Source: org_study_id